The Metropolitan is a native of New Hampshire, having been born in Portsmouth. He is one of four children born to Dennis and Mary (Kapsimalis) Chronopoulos who had immigrated to the United States from Olympia, Greece. After his primary and high school education, he served with distinction in the United States Marine Corps during the Korean conflict. In the autumn of 1954 he enrolled at Holy Cross Greek Orthodox Seminary in Brookline, Massachusetts. Upon his graduation in 1960, he undertook graduate studies at the Theological School of Halki.

Archbishop Iakovos next assigned Fr. Isaiah to Hellenic College and Holy Cross School of Theology as the Director of Student Life in August of 1971. Taking a leave of absence from his duties in February 1975, he enrolled as a graduate student at the School of Theology at the University of Thessaloniki, fulfilling requirements for the recognition of his master's degree in theology. He returned to the United States in July of that year and continued in the capacity of Dean of Students.

In September 1976 he was appointed the Dean of Administrative Affairs, concurrent with his position as Dean of Students. In October 1977 he assumed additional duties as the interim pastor at Saint Nicholas Church in Portsmouth, New Hampshire. Relinquishing all of these positions in March 1979, he was assigned as the Chancellor of the Diocese of Chicago under His Grace, BishopIakovos of Chicago.

Metropolitan Isaiah was elected to the episcopacy by the Holy Synod of the Ecumenical Patriarchate in Istanbul (Constantinople), Turkey, on April 10, 1986. He was consecrated a bishop on May 25, 1986, at Holy Trinity Cathedral in New York City, and was given the title of Bishop of Aspendos, a former Christian city in southwestern Asia Minor. In September 1986, Archbishop Iakovos assigned him as the Chancellor of the Archdiocese in New York. Bishop Isaiah continued to function in this capacity until June 23, 1992, when he was elected Bishop of Denver by the Ecumenical Patriarchate, taking the new title on June 24, 1992, at special ceremonies in the Archdiocesan Chapel of St. Paul. He was enthroned as Bishop of Denver on September 10, 1992, at the Greek Orthodox Cathedral of the Assumption of the Virgin Mary in Denver, Colorado.

On November 24, 1997, the Holy and Sacred Synod of the Ecumenical Patriarchate elevated him to Metropolitan of Proikonisos and Presiding Hierarch of the Greek Orthodox Diocese of Denver. Metropolitan Isaiah was also appointed as President of Hellenic College/Holy Cross Greek Orthodox School of Theology on July 1, 1997, by His Eminence Archbishop Spyridon of America. He accepted a one-year term which officially ended on August 14, 1998.

On December 20, 2002, the Ecumenical Patriarchate elevated the status of the Diocese to a Metropolis, and elected Metropolitan Isaiah as Metropolitan of Denver.